Preliminary investigations demonstrate that specifically cytotoxic effector cells can be generated by in vitro coculture of murine lymphocytes with syngeneic cells derived from spontaneously occurring mammary tumors. The objectives of the current proposal are to further characterize this in vitro model system, to utilize it to ascertain the basic mechanisms underlying the in vivo immune responses to syngeneic mammary tumors, and to determine optimal conditions for obtaining successful therapeutic effects when lymphocytes sensitized in vitro are transferred into tumor bearing mice. In initial studies I will perform experiments designed to determine the role of T lymphocytes, B lymphocytes and macrophages in the recognition and destruction of tumor cells in this in vitro system and to determine the antigenic specificity of the cytotoxic effector cells generated in vitro. Guided by the information obtained from these initial studies I will utilize lymphocytes sensitized in vitro against syngeneic mammary tumor cells to achieve adoptive immunotherapy. I have also proposed experiments designed to study the mechanisms underlying the immunotherapeutic effects of the immune effector cells by determining the fate of these cells after transfer into tumor bearing mice.